The present invention relates to a series of new 2-penem-3-carboxylic acid derivatives, to their preparation and to their use as antibiotics for the treatment of a variety of diseases caused by bacteria, both Gram-positive and Gram-negative.
The penicillins form a well-known class of antibiotics, which have found considerable use in human and animal therapy for many years. Indeed, benzyl penicillin, which was the first of the antibiotics to come into general therapeutic use, is still widely used today. Chemically, the penicillins have in common a .beta.-lactam-type structure commonly referred to as "penam", which has the following formula: ##STR4##
However, although the penicillins still form a valuable weapon in the pharmaceutical armory, the development of new, and often penicillin-resistant, strains of pathogenic bacteria has increasingly made it necessary to search for new types of antibiotic. Recently, some interest has been shown in compounds having a penem structure, that is compounds having a double bond between the carbon atoms in the 2- and 3-positions of the basic penam structure. The penem structure is as follows: ##STR5##
These penam and penem structures form the basis for the semi-systematic nomenclature of the penicillin derivatives and this nomenclature is generally accepted by those skilled in the art throughout the world and is used herein, the numbering system being that illustrated on the above structures.
Of the penem derivatives discovered in recent years, a compound thought to be of particular value is 2-[(2-aminoethyl)thio]-6-(1-hydroxyethyl)penem-3-carboxylic acid, which has the formula: ##STR6## This compound was disclosed by name in British Patent Specification No. 2013674A, and in U.S. Pat. No. 4,168,314. However, valuable though the activity of 2-[(2-aminoethyl)thio]-6-(1-hydroxyethyl)penem-3-carboxylic acid is, we have now discovered a series of related compounds having an antibiotic activity, particularly against Gram-negative bacteria, greater than that of this known compound; moreover, there are indications that the acute toxicities of the compounds of the present invention are significantly lower than that of the prior art compound.